{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:59:02Z","timestamp":1760266742162},"reference-count":32,"publisher":"American Diabetes Association","issue":"3","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,3,1]]},"abstract":"<jats:p>Tissue-specific expression of Fas-ligand (Fas-L) can provide immune privilege by inducing apoptosis of \u201cinvading\u201d lymphocytes expressing Fas. However, accelerated diabetes has been reported in transgenic mice expressing Fas-L in islets (RIP-Fas-L) as a result of Fas-dependent fratricide of \u03b2-cells after transfer of diabetogenic clones. Here we studied whether Fas-L could protect islets from autoaggressive CD8 lymphocytes in a transgenic model of virally induced diabetes (RIP-LCMV-NP transgenic mice), in which the autoaggressive response is directed to a viral nucleoprotein (NP) expressed as a transgene in \u03b2-cells. Indeed, disease incidence after viral (lymphocytic choriomeningitis virus [LCMV]) infection was reduced by \u223c30%, which was associated with a decrease of autoaggressive CD8 NP-specific lymphocytes in islets and pancreatic draining lymph nodes. However, surprisingly, a high degree (50%) of diabetes was seen in mice that expressed only Fas-L but not the viral transgene (NP) in \u03b2-cells after infection with LCMV. This was due to induction of Fas on \u03b2-cells after LCMV infection of the pancreas, resulting in Fas\/Fas-L\u2013mediated fratricide. Thus, although Fas-L can lend some immune privilege to islet cells, local virus-induced inflammation will induce Fas on \u03b2-cells, leading to their mutual destruction if Fas-L is present. Expression of Fas-L therefore might not be protective in situations in which viral inflammation can be expected, resulting in Fas induction on the targeted cell itself.<\/jats:p>","DOI":"10.2337\/diabetes.53.3.591","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"591-596","update-policy":"http:\/\/dx.doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":13,"title":["Virally Induced Inflammation Triggers Fratricide of Fas-Ligand\u2013Expressing \u03b2-Cells"],"prefix":"10.2337","volume":"53","author":[{"given":"Urs","family":"Christen","sequence":"first","affiliation":[{"name":"Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rima","family":"Darwiche","sequence":"additional","affiliation":[{"name":"St. Vincent\u2019s Institute, Fitzroy, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen E.","family":"Thomas","sequence":"additional","affiliation":[{"name":"St. Vincent\u2019s Institute, Fitzroy, Victoria, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Wolfe","sequence":"additional","affiliation":[{"name":"Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Evelyn","family":"Rodrigo","sequence":"additional","affiliation":[{"name":"Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Chervonsky","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias G.","family":"von Herrath","sequence":"additional","affiliation":[{"name":"Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, San Diego, California"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031217043591500_R1","doi-asserted-by":"crossref","unstructured":"Kaplan HJ, Leibole MA, Tezel T, Ferguson TA: Fas ligand (CD95 ligand) controls angiogenesis beneath the retina. 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